Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5′-phosphatase isoform that partners with the Grb2 adapter protein

SH2-containing inositol 5 ' -phosphatase (SHIP) modulates the activation of immune cells after recruitment to the membrane by Shc and the cytoplasmic tails of receptors. A novel SHIP Isoform of approximately 104 kd expressed In primitive stem cell populations (s-SHIP) Is described. It was found that s-SHIP is expressed In totipotent embryonic stem cells to the exclusion of the 145-kd SHIP Isoform expressed in differentiated hematopoietic cells. s-SHIP Is also expressed In primitive hematopoietic stem cells, but not in lineage-committed hematopoietic cells. In embryonic stem cells, s-SHIP partners with the adapter protein Grb2 without tyrosine phosphorylation and is present constitutively at the cell membrane. It is postulated that s-SHIP modulates the activation threshold of primitive stem cell populations. (C) 2001 by The American Society of Hematology.